巨噬细胞相关GBP4作为克罗恩病的新生物标志物:来自WGCNA、孟德尔随机化和免疫组织化学验证的见解

IF 3.3 4区 医学 Q3 CHEMISTRY, MEDICINAL
Heng Shi, Sisi Liu, Qin Peng
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引用次数: 0

摘要

克罗恩病(CD)是一种复杂的炎症性肠病,其机制尚不完全清楚。方法:利用基因表达Omnibus (gene expression Omnibus, GEO)数据库中的基因表达数据(GSE17928522),将1135名CD患者与180名健康对照者进行比较,以确定基因表达谱的改变。免疫浸润分析评价免疫细胞亚群的变化。采用加权基因共表达网络分析法(Weighted Gene Co-expression Network Analysis, WGCNA)构建基因共表达网络,鉴定巨噬细胞相关模块。孟德尔随机化被用来验证巨噬细胞的因果作用。为了离体验证,我们对6例伴有回肠或结肠病变的CD患者的结肠组织样本进行了GBP4蛋白表达的免疫组织化学染色。来自同一患者的非病变组织作为个体内对照,以尽量减少患者之间的差异。结果:我们的分析揭示了CD微环境中免疫细胞亚群,特别是巨噬细胞的显著变化。发现巨噬细胞相关模块,其中GBP4是一个关键基因。免疫组织化学染色证实,与对照组相比,CD组织样本中GBP4的表达存在差异。讨论:这项多模式研究证实GBP4是一种新的巨噬细胞相关的CD生物标志物,并得到因果孟德尔随机化和免疫组织化学验证的支持。WGCNA和遗传证据的整合强化了巨噬细胞失调在CD发病机制中的作用。局限性包括基因组数据的群体偏倚和较小的验证队列,但不同方法的一致性强调了GBP4作为治疗靶点的潜力。结论:我们的研究结果突出了GBP4作为一种新的潜在生物标志物和CD治疗靶点,为该疾病的免疫介导机制提供了新的见解。这些结果有助于更好地了解乳糜泻的发病机制,并可能导致新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Macrophage-Related GBP4 as a Novel Biomarker for Crohn's Disease: Insights from WGCNA, Mendelian Randomization, and Immunohistochemical Validation.

Introduction: Crohn's disease (CD) is a complex inflammatory bowel disorder with incompletely understood mechanisms. This study aimed to identify novel biomarkers and elucidate macrophage-related pathogenesis in CD.

Methods: Using gene expression data (GSE17928522) from the Gene Expression Omnibus (GEO) database, we compared 1135 CD patients with 180 healthy controls to identify altered gene expression profiles. Immune infiltration analysis was conducted to evaluate changes in immune cell subpopulations. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct gene co-expression networks and identify macrophage-associated modules. Mendelian randomization was used to validate the causal role of macrophages. For ex vivo validation, immunohistochemical staining of GBP4 protein expression was performed in colonic tissue samples from 6 CD patients (with ileal or colonic lesions). Non-lesional tissues from the same patients served as intra-individual controls to minimize inter-patient variability.

Results: Our analysis revealed significant changes in immune cell subpopulations, particularly macrophages, within the CD microenvironment. A macrophage-associated module was identified, with GBP4 emerging as a critical gene. Immunohistochemical staining confirmed differential expression of GBP4 in CD tissue samples compared to controls.

Discussion: This multi-modal study establishes GBP4 as a novel macrophage-associated biomarker for CD, supported by causal Mendelian randomization and immunohistochemical validation. The integration of WGCNA and genetic evidence strengthens the role of macrophage dysregulation in CD pathogenesis. Limitations include population bias in genomic data and small validation cohorts, but the consistency across methodologies underscores GBP4's potential as a therapeutic target.

Conclusion: Our findings highlight GBP4 as a novel potential biomarker and therapeutic target in CD, providing insights into the immune-mediated mechanisms underlying the disease. These results contribute to a better understanding of CD pathogenesis and may lead to new therapeutic strategies.

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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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